| Autor: |
Subirada PV; Instituto Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba 5016, Argentina., Tovo A; Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Universidad Nacional de Córdoba, Córdoba 5016, Argentina., Vaglienti MV; Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Universidad Nacional de Córdoba, Córdoba 5016, Argentina., Luna Pinto JD; Centro Privado de Ojos Romagosa, Fundación VER, Córdoba 5000, Argentina., Saragovi HU; Lady Davis Research Institute-Jewish General Hospital, Center for Experimental Therapeutics, Department of Pharmacology and Therapeutics, Department of Ophthalmology and Vision Sciences, McGill University, Montreal, QC H3T 1E2, Canada., Sánchez MC; Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Universidad Nacional de Córdoba, Córdoba 5016, Argentina., Anastasía A; Instituto Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba 5016, Argentina.; Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba 5016, Argentina., Barcelona PF; Departamento de Bioquímica Clínica, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Universidad Nacional de Córdoba, Córdoba 5016, Argentina. |
| Abstrakt: |
Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75 NTR ) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75 NTR is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75 NTR knockout mice (p75 NTR KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75 NTR antagonist in wild type mice with CNV phenocopied the results of the p75 NTR KO mice. Our results demonstrate that p75 NTR is etiological in the development of CNV. |
